基因编码的光传感器使得,鱼和老鼠中的多巴胺能够快速和精确地检测到
Fangmiao Sun1, Jianzhi Zeng2, Miao Jing2
1State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 Beijing, China; PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China.
Cell
|July 16, 2018
概括
研究人员开发了新的基因编码多巴胺 (DA) 传感器,称为GRAB_DA,以准确地实时测量DA波动. 这些传感器允许在复杂的行为过程中详细观察动物的DA信号.
科学领域:
- 神经科学
- 分子生物学
- 生物化学
背景情况:
- 多巴胺 (DA) 是调节许多生理和病理过程的关键神经递质.
- 准确地测量高时空精度的DA动态,特别是在复杂的行为过程中,仍然是一个重大挑战.
研究的目的:
- 开发和验证新的基因编码传感器以实时高精度测量细胞外多巴胺.
- 在自然行为过程中,在各种模型生物中研究多巴胺信号.
主要方法:
- 开发基因编码的基于GPCR激活的DA (GRAB_DA) 传感器.
- 在体外测定传感器性能,包括亲和力,动力学和特异性.
- 使用电生理学,光遗传学和行为范式在脑切片,,鱼和自由行为小鼠中的体内验证.
主要成果:
- 通过GRAB_DA传感器,显现出较大的光度增加 (ΔF/F0~90%) 与亚细胞分辨率和亚秒运动.
- 传感器对多巴胺具有很高的亲和力 (从纳米到微米) 和很好的分子特异性.
- 在大脑切片和行为动物中成功检测到由单个电刺激引起的内源性DA释放.
结论:
- GRAB_DA传感器提供了一个强大的空间时间精确测量多巴胺动力学工具.
- 这些传感器有助于研究多巴胺在各种模型生物中的复杂行为.
- 这种发展代表了神经化学传感技术的重大进步.
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